The Upper Airway, Asthma and Sleep Disorders in Children

Athanasios Kaditis, MD
University of Athens School of Medicine and Aghia Sophia Children's Hospital
Athens, Greece

Snoring is the most common clinical manifestation of obstructive sleep-disordered breathing (1). Moreover, wheezing is the most characteristic symptom of lower airway obstruction, a disorder that is frequently virus-induced and with or without an asthmatic component (2). This presentation will summarize published evidence on the interaction between obstructive sleep-disordered breathing and recurrent wheezing or asthma in childhood, and their effects on sleep quality.

Obstructive sleep-disordered breathing and its effects on sleep quality
The term "obstructive sleep-disordered breathing" describes a spectrum of abnormal breathing patterns during sleep characterized by snoring and increased respiratory effort (3). Enlarged tonsils and adenoid, or obesity, are common abnormalities that can increase resistance to airflow and the tendency of the pharyngeal airway to collapse during inspiration (pharyngeal collapsibility) (4, 5). Although EEG arousal is an important defence mechanism against airway obstruction, it has also a negative impact on sleep architecture and quality (6). As a result, increased frequency of daytime sleepiness, inattention, hyperactivity, cognitive problems and academic difficulties have been demonstrated in children with obstructive sleepdisordered breathing (7, 8).

Effects of wheezing on sleep quality
In a cross-sectional pediatric study, subjects with parental report of wheezing in the last 12 months had a 2-fold higher risk for difficulty falling asleep, a 4-fold higher risk for restless sleep and a 5-fold higher risk for daytime sleepiness as compared to those without wheezing (9).

Association of sleep-disordered breathing with recurrent wheezing or asthma
Several studies have demonstrated more frequent snoring in asthmatic children when compared to non-asthmatic control subjects (10-12). Redline and colleagues have shown that usual cough, occasional and persistent wheeze, and doctor-diagnosed asthma are significant risk factors for the presence of an apnea-hypopnea index greater than 10 episodes/h (13). Tonsillar hypertrophy mediates at least in part the relationship between recurrent wheezing or asthma and obstructive sleep-disordered breathing in childhood (14).

Pathogenic links between obstructive sleep-disordered breathing and recurrent wheezing or asthma
It has been speculated that the epidemiologic association between recurrent wheezing or asthma and obstructive sleep-disordered breathing is the result of both conditions sharing common pathogenic pathways (13). Airway oxidative stress and inflammation related to leukotrienes have been implicated in the pathogenesis of both obstructive sleep-disordered breathing and recurrent wheezing. Increased concentrations of leukotriene B4, cysteinyl leukotrienes and isoprostane-8, a marker of oxidative stress, have been found in the exhaled breath condensate of children with episodic or persistent asthma (15-18). Similar findings have been demonstrated in pediatric patients with obstructive sleep-disordered breathing (19, 20).

Of interest, sleep apneic children have increased activity and content of cysteinyl leukotrienes in adenoid and tonsils (21, 22). Cysteinyl leukotrienes induce a proliferative response in tonsillar cell cultures and they may be implicated in the pathogenesis of adenotonsillar hypertrophy (23). Airway inflammation and especially oxidative stress, could enhance the biosynthesis of cysteinyl leukotrienes within the pharyngeal lymphoid tissues promoting adenotonsillar enlargement and deterioration of upper airway obstruction.